Benzoxazole and benzodiazole UV-A sunscreens

ABSTRACT

The present invention relates to 1,3-benzoxazole or benzodiazole UV-A sunscreens and to compositions, in particular topical compositions, containing the above UV-A sunscreens.

This application is the National Stage of International Application No.PCT/EP2003/003634, filed Apr. 8, 2003.

The present invention relates to novel UV-A sunscreens and tocompositions, in particular topical compositions, containing the aboveUV-A sunscreens.

Depending on the wavelength, UV rays are designated as UV-A rays(320-400 nm) and UV-B rays (280-320 nm). The damaging action of the UVrays on the human skin increases with decreasing wavelength andincreasing duration of exposure. UV rays can thus cause skin damage, itbeing possible for UV-B radiation to cause sunburn (erythema) up to verysevere skin burns. Very frequent and unprotected irradiation of the skinwith sunlight also leads to a loss in skin elasticity and to increasedwrinkle formation and on the whole to premature aging of the skin. Inextreme cases pathological skin changes up to skin cancer can occur.

The UV-A radiation causes a rapid, weak direct pigmentation of the skin.UV-A rays penetrate into deeper skin layers and there can accelerate theaging process of the skin. The UV-A radiation can furthermore elicitphototonic or photoallergic skin reactions. Confirmed relationshipsexist between UV-A exposure and increased risk of skin cancer. Accordingto the position of their absorption maxima, UV absorbers for cosmeticand dermatological preparations are divided into UV-A and UV-Babsorbers. While there are a large number of safe and effective UV-Babsorbers, UV-A absorbers suitable for the protection of human skin arerare and, moreover, affected by serious disadvantages

EP-A1-669 323, DE-3644633, DE 4107439 disclose, for instance,benzo-diazoles, -thiazoles and/or benzoxazoles absorbing in the UV-Arange. The compounds according to these prior art documents, whichcompounds strongly differ in their chemical structure from thoseaccording to the present invention, show low liposolubility. This is aserious drawback since UV-sunscreens must usually be incorporated intothe lipid phase of the cosmetic and/or dermatological composition inorder to assure an optimal absorption into the skin.

Furthermore, the UV-A sunscreens of the cited prior art usually do notshow photostability. This is an additional drawback since they loosetheir activity when exposed to the sun light.

The object at the root of the present invention is to provide UV-Asunscreens overcoming the drawbacks mentioned above, i.e. UV-Asunscreens with good liposolubility and high photostability.

This object is achieved by providing compounds of general formula I

wherein

-   R¹ and R² are, independently from each other, hydrogen; halogen;    hydroxy; (C₁-C₂₀)-alkyl; (C₂-C₂₀)-alkenyl; or (C₁-C₂₀)-alkoxy;-   X is oxygen or an imino group, optionally substituted with R¹;-   R³ and R⁴ are, independently from each other, cyano; —COOR⁵; —COR⁶;    —CONH₂; —CONHR⁷; or —CONR⁸R⁹;-   R⁵, R⁶, R⁷, R⁸ and R⁹ are, independently from each other, hydrogen;    (C₁-C₂₀)-alkyl, wherein one or more methylene groups are optionally    replaced by oxygens; (C₁-C₂₀)-haloalkyl; (C₂-C₂₀)-alkenyl,    optionally substituted by tri-(C₁-C₅)-alkylsilyl or triphenylsilyl    or a group-Si[CH₃]_(n)[OSi(CH₃)₃]_(3-n), wherein n is 0, 1, 2 or 3.

The compounds of general formula I are valuable, photostable productswhich have their absorption maxima in the UV-A range. They are moreoverlipophilic and, therefore, suitable for being incorporated into thelipid phase of sun screen formulations.

As used herein, C₁-C₂₀-alkyl denotes straight chain or branched chainalkyl residues with 1 to 20 carbon atoms, such as methyl, ethyl, propyl,isopropyl, thexyl (=1,1,3,3-tetramethyl-butyl), 1,1,2-trimethylpropyl,n-butyl, sec.-butyl, tert.-butyl, pentyl, neopentyl, hexyl,2-ethyl-hexyl, octyl and the like. C₁-C₈-Alkyl groups are preferred.

C₂-C₂₀-Alkenyl denotes straight chain or branched chain alkenyl residueswith 2 to 20 carbon atoms and containing at least one C—C double bond,such as vinyl, allyl, 2-butenyl, methallyl, 2-penten-3-yl, 3-hexen-2-yl,3-hepten-2-yl, 3-octen-2-yl, 1-octen-3-yl and 2-octen-1-yl.C₂-C₈-Alkenyl groups are preferred.

Examples of “(C₁-C₂₀)-alkyl wherein one or more methylene groups areoptionally replaced by oxygen” are methoxymethyl, 4-oxa-hexyl,4,7-dioxa-nonyl and 4,7,10-trioxadodecyl.

A tri-(C₁-C₅)-alkylsilyl moiety is a group —SiR^(a)R^(b)R^(c), whereinR^(a), R^(b) and R^(c) each independently are C₁-C₅-alkyl. Preferredsilyl moieties are trimethylsilyl, triethylsilyl, tripropylsilyl,triisopropylsilyl, dimethyl-tert.-butyl-silyl, dimethyl-thexyl-silyl,and the like. Preferred trisubstituted silyl groups are trimethylsilyl,triethysilyl and triphenylsilyl.

The compounds of general formula I can be prepared by condensation of acompound of general formula IIIa (if X is O) or IIIb (if X is NH or NR¹)

with a compound of general formula IV

wherein R¹, R², R³ and R⁴ have the meanings given above.

The condensation with heterocyclic ring formation is carried out in thepresence of an acidic catalyst. Any strong anorganic or organic acid,such as H₂SO₄, HCl, H₃PO₄, H₃BO₃, or p-toluenesulfonic acid, can be usedfor this purpose. The water formed by the reaction can be removed byazeotropic destination (e.g using toluene or CH₂Cl₂ as a solvent) or bymeans of a hygroscopic agent such as P₂O₅. The reaction temperature mayvary between 0° C. and 200° C. and depends on the concentration andstrength of the acid.

The starting material of general formula IV can be obtained by means ofa Knoevenagel condensation, i.e., by reacting a compound of generalformula V, optionally in the form of an ester built with an alkanol,with a compound of general formula VI:

The condensation may take place, e.g., under azeotropic destination inthe presence of a solvent capable of forming an azeotrope with water(e.g. toluene or chloroform) and of a water separator. Acids and/orbases can be used as catalyst: acids like acetic acid, benzoic acid,toluenesulfonic acid, sulfuric acid, BF₃, or bases like pyridine,piperidine or morpholine. Anhydrides like P₂O₅ can also catalyze thereaction.

A compound of general formula I can also be manufactured by invertingthe order of the above steps, i.e. by reacting a compound of generalformula VII with a compound of general formula VI

A compound of general formula VII, on its turn, can be obtained byreacting a compound of general formula IIIa (X═O) or IIIb (X═NH or NR¹)with a compound of general formula V. The general reaction conditionsare the same as for the ring closure described above.

Preferred compounds of formula I are those wherein X is O. Furthermore,particularly preferred compounds are those wherein R¹ and R² arehydrogen, as well as those wherein R³ is cyano and R⁴ is —COOR⁵.Examples of such compounds are:

-   2-Cyano-3-{4-[5-tert.-butyl-benzoxazol-2-yl]-phenyl}-acrylic acid    2-ethylhexyl ester and-   2-Cyano-3-{4-benzoxazol-2-yl-phenyl}-acrylic acid 2-ethylhexyl    ester.

Compounds wherein R³ and R⁴ are independently from each other —COOR⁵ arealso preferred. Examples of such compounds are:

-   2-(4-Benzoxazol-2-yl-benzylidene)-malonic acid diethyl ester;-   2-(4-Benzoxazol-2-yl-benzylidene)-malonic acid dibutyl ester;-   3-{4-Benzoxazol-2-yl-phenyl}-2-propionyl-acrylic acid 2-ethylhexyl    ester;-   2-(4-[6-Hydroxy-benzoxazol-2-yl]-benzylidene)-malonic acid diethyl    ester;-   2-(4-[6-{2-Ethyl-hexyloxy}-benzoxazol-2-yl]-benzylidene)-malonic    acid diethyl ester; and-   2-(4-{6-[2-(2-Ethoxy-ethoxy)-ethoxy]-benzoxazol-2-yl}-benzylidene)-malonic    acid diethyl ester.

In another aspect, the present invention relates to substitutedpolysiloxanes of the general formula(H₃C)₃Si—(B)_(q)—OSi(CH₃)₃   IIwherein

-   B is a residue selected from the group consisting of B1, B2, B3, B4    and B5;

-   W is a residue from the group consisting of W1, W2 and W3

wherein X, R1, R2, R3 and R4 are as defined above; Y is oxygen,(C₁-C₂₀)-alkylene, (C₂-C₂₀)-alkenylene, or —O—(C₁-C₂₀)-alkylene; and Y′is (C₁-C₂₀)-alkylene or (C₂-C₂₀)-alkenylene.

-   q is an integer between 1 and 400 and represents the sum of residues    B1 to B5 in arbitrary sequence,    wherein at least one B is B1, B2, B3 or B4, the ratio    (B1+B2+B3+B4)/(B1+B2+B3+B4+B5)    not exceeding 0.6.

Preferred polysiloxanes of formula II are those wherein q is in therange between 2 and 100. Particularly preferred polysiloxanes of formulaII are those for which the ratio (B1+B2+B3+B4)/(B1+B2+B3+B4+B5) isbetween 0.01 and 0.4.

A preferred polysiloxane of formula II is

The compounds of general formula II can be prepared by grafting acompound of formula VIII

onto a poly-(methyl-hydrosiloxane)

wherein m+p=q,

q being as defined above

and the different residues are in arbitrary sequence

It is evident that the molar ratio of the reaction partners isdetermined by the hydrid content, i.e. content of groups —Si[H][CH₃]—O—, of compound IX.

Typically, the reaction takes place in the neat polysiloxane or in apolysiloxane solution in, e.g.) toluene, THF or isopropanol The reactionmay take place in the presence of homogeneous catalysts (Karstedtcatalyst) or a heterogeneous platin catalyst (chloroplatinic acid), at atemperature between 40 and 150° C., preferably between 60 and 100° C.,and for a period of time varying between 2 and 48 hours.

The compounds of formulae VIIIaa and VIIIab can be obtained by treatinga compound of formula VII wherein R² is OH with a) proparagyl bromide orb) with allylbromide, respectively, using a base (e.g. KOH or K₂CO₃) at50 to 150° C. in a polar aprotic solvent like, e.g., N-methylpyrrolidoneor butanone. This new compound of formula VIIaa ox VIIab can be treatedwith a compound VI as described above. The compounds of formulae VIIbaand VIIIbb can be obtained accordingly under the above conditionsstarting from compound VII wherein X is NH or NR¹. The compounds offormulae VIIIca and VIIIcb can be obtained by treating a compound offormula VI wherein R³ is CN and R⁴ is COOR⁵ (compound VI′) to give acompound of formula VI″ or VI″′, respectively, before reacting them withcompound VII as described above.

To obtain compound VI″, compound VI′ treated with dry HCl or conc. H₂SO₄at room temperature followed by addition of propynol or propenol,respectively, and hydrolysis of the immonium salt intermediate. CompoundVI″′ is formed from compound VI′ by transestenfication, using excess ofpropynol or propenol, respectively.

A further aspect of the present invention concerns the use of one ormore compounds of formulae I and/or II as an UV-A screening agent. Inparticular, the compounds of general formulae I and/or II are suitablefor protecting human skin and/or human hair from UV-A irradiation, aswell as for protecting UV sensitive plastic materials and medicinalproducts.

It is still a further aspect of the present invention to provide acomposition, in particular a topical composition, containing one or morecompounds of formulae I and/or II and at least one pharmaceuticallyand/or cosmetically acceptable excipient.

The compositions comprising one or more compounds of formulae I or IIare particularly suitable for topical applications onto human skinand/or hair. Accordingly, they are suitable for protecting materialsthat are sensitive to ultraviolet radiation, in particular solarradiation, and comprises an effective photoprotective amount of at leastone of the compounds of formulae I or II. In a preferred embodiment ofthe invention, such compositions are suitable for protecting human skinand/or human hair against the deleterious effects of UV-radiation. Inthis case, the compositions according to the invention are cosmeticand/or dermatological compositions which comprise, as a carrier,topically applicable, cosmetically acceptable vehicles and diluents.

If appropriate, additional UV-A and UV-B screening agents may be addedinto the cosmetic and/or dermatological composition of the presentinvention. The combination of different UV filters may also showsynergistic effects.

The total amount of UV screening agents, i.e. of the compounds ofgeneral formula I and/or II and additional UV-A/B screening agents, isnot critical. Suitable amounts may vary between 0.5 and 20%, preferablybetween 0.5and 12%, by weight of the total amount of the composition.

Suitable UV-B screening agents which maybe added to the UV-A screeningagents of the present invention are the following organic and inorganiccompounds:

-   -   acrylates, such as 2-ethylhexyl-2-cyano-3,3-diphenylacrylate        (octocrylene, PARSOL® 340), ethyl 2-cyano-3,3-diphenylaciate and        the like;    -   camphor derivatives such as 4-methyl benzylidene camphor        (PARSOL® 5000), 3-benzylidene camphor, camphor benzalkonium        methosulfate, polyacrylamidomethyl benzylidene camphor, sulfo        benzylidene camphor, sulphomethyl benzylidene camphor,        therephthalidene dicamphor sulfonic acid and the like;    -   cinnamate derivatives such as octyl methoxycinnamate (PARSOL®        MCX), ethoxyethyl methoxycinnamate, diethanolamine        methoxycinnamate (PARSOL® Hydro), isoamyl methoxycinnamate and        the like, as well as cinnamic acid derivatives bound to        siloxanes;    -   p-aminobenzoic acid derivatives, such as p-aminobenzoic        acid)2-ethylheyl p-dimethylaminobenzoate, N-oxypropylenated        ethyl p-aminobenzoate, glyceryl p-aminobenzoate;    -   benzophenones, such as benzophenone-3, benzophenone-4,2,2′,        4,4′-tetrahydroxy-benzophenone,        2,2′-dihydroxy-4,4′-dimethoxybenzophenone and the like;    -   esters of benzalmalonic acid such as        di-(2-ethylhexyl)-4-methoxybenzalmalonate;    -   esters of 2(4-ethoxy-anilinomethylene)-propandioic acid, such as        2-(4-ethoxy-anilinomethylene)-propandioic acid diethyl ester        (EP-A2-0895 776);    -   organosiloxane compounds containing benzmalonate groups as        described in the European Patent Publications EP-B1-0358584,        EP-B1-0538431 and EP-A1-0709080;    -   drometrizole trisiloxane (Mexoryl XL);    -   pigments such as microparticulated TiO₂, and the like, the term        “microparticulated” referring to a particle size from about 5 nm        to about 200 nm, particularly from about 15 nm to about 100 nm.        The TiO₂ particles may also be coated by metal oxides such as        aluminum or zirconium oxide, or by organic coatings such as        polyols, methicone, aluminum stearate, alkyl silane and the        like. Such coatings are well known in the art.    -   Imidazole derivatives such as, e.g., 2-phenyl benzimidazole        sulfonic acid and its salts (PARSOL®HS). Salts of 2-phenyl        benzimidazole sulfonic acid are, e.g., alkali salts such as        sodium- or potassium salts, ammonium salts, morpholine salts,        salts of primary, sec. and tert. amines like monoethanolamine        salts, diethanolamine salts and the like.    -   Salicylate derivatives such as isopropylbenzyl salicylate,        benzyl salicylate, butyl salicylate, octyl salicylate (NEO        HELIOPAN OS), isooctyl salicylate or homomenthyl salicylate        (homosalate, HELIOPAN) and the like.    -   Triazone derivatives such as octyl triazone (UVINUL T-150),        dioctyl butamido triazone (UVASORB HEB) and the like.

Suitable conventional UV-A screening agents which may be added to theUV-A screening agents of the present invention are the following organicand inorganic compounds:

-   -   Dibenzoylmethane derivatives such as        4-tert.-butyl-4′-methoxydibenzoyl-methane (PARSOL® 1789),        dimethoxydibenzoylmethane, isopropyldibenzoylmethane and the        like;    -   benzotriazole derivatives such as        2,2′-methylene-bis-(6-(2H-benzotriazole-2-yl)-4-(1,1,3,3,-tetraznethylbutyl)-phenol        (TINOSORB M) and the like;    -   phenylene-1,4-bis-benzimidazolsulfonic acids or salts such as        2,2-(1,4-phenylene)-bis-(1H-benzimidazol-4,6-disulfonic acid)        (Neoheliopan AP);    -   amino substituted hydroxybenzophenones such as        2-(4-diethylamino-2-hydroxy-benzoyl)-benzoic acid hexylester as        described in European Patent Publication EP 1046391;    -   pigments such as microparticulated ZnO and the like. The term        “microparticulated” refers to a particle size from about 5 nm to        about 200 nm, particularly from about 15 nm To about 100 nm. The        ZnO particles may also be coated by metal oxides such as, e.g.,        aluminum or zirconium oxides or by organic coatings such as e.g.        polyols, methicone, aluminum stearate, alkyl silane. Such        coatings are well known in the art.

Because dibenzoylmethane derivatives are photolabile UV-A screeningagents, it may be desirable to photostabilize them. Thus, the term“conventional UV-A screening agent” also refers to dibenzoylmethanederivatives such as e.g. PARSOL® 1789 stabilized by, e.g.,

-   -   3,3-diphenylacrylate derivatives as described in EP-B1-0514491        and EP-A1-0780119;    -   benzylidene camphor derivatives as described in U.S. Pat. No.        5,605,680;    -   organosiloxanes containing benzmalonate groups as described in        EP-B1-0358584, EP-B1-053843 and EP-A1-0709080.

The compositions of the invention can also contain usual cosmeticadjuvants and additives, such as preservatives/antioxidants, fattysubstances/oils, water, organic solvents, silicones, thickeners,softeners, emulsifiers, additional sunscreens, antifoaming agents,moisturizers, fragrances, surfactants, fillers, sequestering agents,anionic, cationic, nonionic or amphoteric polymers or mixtures thereof,propellants, acidifying or basifying agents, dyes, colorants, pigmentsor nanopigments, in particular those suitable for providing anadditional photoprotective effect by physically blocking out ultravioletradiation, or any other ingredients usually formulated into cosmetics,in particular for the production of sunscreen/antisun compositions. Thenecessary amounts of the cosmetic and dermatological adjuvants andadditives can, based on the desired product, easily be chosen by theskilled person.

Particularly preferred antioxidants are those chosen from the groupconsisting of amino acids (e.g. glycine, histidine, tyrosine,tryptophane) and their derivatives, imidazole (e.g urocanic acid) andderivatives, peptides such as D,L-carnosine, D-carnosine, L-carnosineand derivatives (e.g. anserine), carotinoids, carotenes (e.g.β-carotene, γ-carotene, lycopene) and derivatives, chlorogenic acid andderivatives, liponic acid and derivatives (e.g. dihydroliponic acid),aurothioglucose, propylthiouracil and other thiols (e.g. thioredoxine,glutathione, cysteine, cystine, cystamine and its glycosyl-, N-acetyl-,methyl-, ethyl-, propyl-, amyl-, butyl- and lauryl-, palmitoyl-, oleyl-,γ-linoleyl-, cholesteryl- and glycerylester) and the salts thereof,dilaurylthiodipropionate, distearylthiodipropionate, thiodipropionicacid and its derivatives (esters, ethers, peptides, lipids, nucleotides,nucleosides and salts) as well as sulfoximine compounds (such asbuthioninsulfoximine, homocysteinsulfoximine, buthioninsulfone, penta-,hexa-, heptathioninsulfoximine) in very low compatible doses (e.g. frompmol to μmol/kg), additional (metal)-chelators (such as α-hydroxyfattyacids, palmic acid, phytinic acid, lactoferrin), α-hydroxyacids (such ascitric acid, lactic acid, malic acid), huminic acid, gallic acid, gallicextracts, bilirubin, biliverdin;, EDTA, EGTA and its derivatives,unsaturated fatty acids and their derivatives (such as γ-linoleic acid,linolic acid, oleic acid), folic acid and its derivatives, ubiquinoneand ubiquinol and their derivatives, vitamine C and derivatives (such asascorbylpalmitate, Mg-ascorbylpbosphate, Na-ascorbylphosphate,ascorbylacetate), tocopherole and derivates (such as vitamine Eacetate), vitamine A and derivatives (vitamine A palmitate) as well asconiferylbenzoat, rutinic acid and derivatives) α-glycosylrutin, ferulicacid, furfurylidenglcitol, carnosin, butylhydroxytoluene,butylhydroxyanisole, trihydoxybutyrophenone, urea and its derivatives;mannose and derivatives, zinc and deivatives (e.g ZnO; ZnSO₄), Selen andderivatives (e.g. selenomethionin), stilbenes and derivatives (such asstilbenoxide, trans-stilbenoxide) and suitable derivatives (salts,esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids)of the named active ingredients.

The preservatives and/or antioxidants-may be present in an amountvarying from about 0.01 wt. % to about 10 wt. % of the total weight ofthe composition. Preferably, the preservatives andlor antioxidants arepresent in an amount varying from about 0.1 wt. % to about 1 wt. %.

The composition according to the present invention may also containemulsifiers. An emulsifier enables two or more immiscible liquids to becombined homogeneously, while increasing the viscosity of thecomposition. Moreover, the emulsifier acts to stabilize the composition.

Emulsifiers that may be used according to the present invention, to formO/W, W/O and/or O/W/O formulations, include sorbitan oleate, sorbitansesquioleate, sorbitan isostearate, sorbitan trioleate,polygyceryl-3-diisostearate, polyglycerol esters of oleic/isostearicacid, polyglyceryl-6 hexaricinolate, polygyceryl-4-oleate,polyglycerol-4 oleate/PBG-8 propylene glycol cocoate, oleamide DEA, TEAmyristate, TEA stearate, magnesium stearate, sodium stearate, potassiumlaurate, potassium ricinoleate, sodium cocoate, sodium tallowate,potassium castorate, sodium oleate, and mixtures thereof Furthersuitable emulsifiers are phosphate esters and salts thereof such ascetyl phosphate, DEA cetyl phosphate, potassium cetyl phosphate, sodiumglyceryl oleate phosphate, hydrogenated vegetable glyceride phosphatesand mixtures thereof Furthermore, one or more synthetic polymers maybeused as emulsifiers. For example, PVP eicosaene copolymer,acrylates/C10-C30 alkyl acrylate crosspolymer, acrylates/stearethmethacrylate copolymer, PEG-22/dodecyl glycol copolymer, PEG-45/dodecylglycol copolymer, and mixtures thereof. The preferred emulsifiers atePVP eicosaene copolymer, acrylates/C10-C30 alkyl acrylate crosspolymer,PEG-20 sorbitan isostearate, sorbitan isostearate, and mixtures thereof.

The emulsifier is present in a total amount varying from about 0.01 wt.% to about 15 wt. %, preferably from about 0.1 wt. % to about 3 wt. %,of the total weight of the composition.

The fatty/oily phase is advantageously chosen from:

-   -   mineral oils and mineral waxes;    -   oils such as triglycerides of caprinic acid or caprylic acid,        preferably castor oil;    -   natural or synthetic oils, preferably esters of carbonic acids        or fatty acids with alcohols, e.g., such as isopropanol,        propyleneglycol or glycerine;    -   alkylbenzoates and    -   silicone oils such as dimethylpolysiloxane, diethylpolysiloxane,        diphenylpolysiloxane and mixtures thereof.

Fatty substances which can be incorporated into the oily phase of thecomposition according to the invention are advantageously chosen fromesters of saturated and/or unsaturated, straight or branched chain alkylcarboxylic acids with 3 to 30 carbon atoms, and saturated and/orunsaturated, straight and/or branched chain alcohols with 3 to 30 carbonatoms, as well as esters of aromatic carboxylic acids and of saturatedand/or unsaturated, straight or branched chain alcohols of 3 to 30carbon atoms. Such esters can advantageously be selected fromoctylpalmitate, octylcocoate, octylisostearate, octyldodecylmyristate,cetylisononanoate, isopropylmyristate, isopropylpalmitate,isopropylstearate, isopropyloleate, n-butylstearate, n-hexyllaurate,n-decyloleat, isooctylstearate, isononylstearate, isononylisononanoate,2-ethyl hexylpalmitate, 2-ethylhexyllaurate, 2-hexyldecylstearate,2-octyldodecylpalmitate, stearylheptanoate, oleyloleate, oleylerucate,erucyloleate, erucylerucate, tridecylstearate, tridecyltrinmellitate, aswell as from synthetic, half-synthetic and natural mixtures of suchesters such as jojoba oil.

Other fatty components suitable for use in the composition according tothe present invention include polar oils such as lecithines and fattyacid triglycerides, namely triglycerinic esters of saturated and/orunsaturated, straight or branched chain carbonic acids with 8 to 24carbon atoms, preferably of 12 to 18 carbon atoms whereas the fatty acidtriglycerides are preferably chosen from synthetic, half synthetic andnatural oils (e.g. cocoglyceride, olive oil, sun flower oil, soybeanoil, peanut oil, rape oil, almond oil, palm oil, coconut oil, castoroil, hydrogenated castor oil, wheat oil, grape oil and others); apolaroils such as linear and/or branched chain hydrocarbons and waxes, e.g.,mineral oils, vaseline (petrolatum); paraffins, squalan and squalen,polyolefines (favored are polydecenes), hydrogenated polyisobutenes andisohexadecanes; dialkyl ethers such as dicaprylylether; linear or cyclicsilicone oils such as cyclomethicone, octametlylcyclotetrasiloxane,cetyldimethicone, hexamethylcyclotrisiloxane, polydimethylsiloxane,poly-(methylphenylsiloxan) and mixtures thereof

Other fatty components which can advantageously be incorporated into thecomposition of the present invention are isoeikosane;neopentylglycoldiheptanoate; propylenglykoldicaprylate/-dicaprate;caprylic-/capric-/diglycerylsuccinate; butylenglykol caprylat/caprat;C12-13 alkyllactate; di-C12-13 alkyltartrate; triisostearin;dipentaerythrityl hexacaprylat/hexacaprate;propylenglykolmonoisostearate; tricaprylin; dimethylisosorbid.Particularly preferred is the use of mixtures of C12-15 alkylbenzoateand 2-ethylhexylisostearate, mixtures of C12-15 alkylbenzoate andisotridecylisononanoate as well as mixtures of C12-15 alkylbenzoate,2-ethylhexylisostearate and isotridecylisononanoate.

The oily phase of the composition according to the present invention canalso contain natural vegetable or animal waxes such as bee wax, chinawax, bumblebee wax and other waxes of insects as well as sheabutter.

The composition according to the present invention may additionallycontain one or more emollients. An emollient provides a softening orsoothing effect on the skin surface and is generally considered safe fortopical use. Emollients also help control the rate of evaporation andthe tackiness of the composition. Preferred emollients include mineraloil, lanolin oil, coconut oil, cocoa butter, olive oil, aloe extracts,jojoba oil, castor oil, fatty acids such as oleic and stearic acid,fatty alcohols such as cetyl and hexadecyl alcohol diisopropyl adipate,benzoic and hydroxybenzoic acid esters of C₉-C₁₅ alcohols, isononyliso-nonanoate, C₁₅-C₅₀ alkanes, mineral oil, silicones such as dimethylpolysiloxane, ethers such as polyoxypropylene butyl ethers andpolyoxypropylene cetyl ethers, and C₂-C₁₅ alkyl benzoates, and mixturesthereof. The most preferred emollients are hydroxybenzoate esters, aloevera, C₁₂₋₁₅ alkyl benzoates, and mixtures thereof.

The emollient is present in an amount varying from about 1 wt. % toabout 20 wt. %, preferably from about 2 wt. % to about 15 wt %, and mostpreferrably from about 4 wt. % to about 10 wt. % of the total weight ofthe composition.

The aqueous phase of the formhulation of the present invention cancontain the usual cosmetic additives such as alcohols, especially loweralcohols, preferably ethanol and/or isopropanol, low alkyl diols orpolyols and their ethers, preferably propyleneglycol, glycerine,ethyleneglycol, ethyleneglycolmonoethyl- or -monobutyl ether,propyleneglycolmonomethyl-, -monoethyl- or -monobutyl ether,diethyleneglycolmonomethyl- or -monoethyl ether and analogue products,polymers, foam stabilisators; electrolytes and, especially, one or morethickeners.

Thickeners that may be used in formulations of the present inventioninclude the family of silicium dioxide, magnesium and/or aluminumsilicates, polysaccharides and their derivatives such as hyaluronicacid, xanthan gum, hydroxypropyl cellulose, acrylate copolymers,preferably a polyacrylate of the family of carbopoles, such ascarbopoles of is type 980, 981, 1382, 2984, 5984.

Moisterizing agents, such as humectants, maybe incorporated into thecomposition according to the present invention to reduce thetrans-epidermal water loss (TEWL) of the horny layer of the skin.Suitable humectants include glycerin, lactic acid, pyrrolidone carbonicacid, urea, polyethylene glycol, polypropylene glycol, sorbitol, PEG-4,and mixtures thereof. Additional suitable moisturizers are polymericmoisturizers of the familiy of water soluble and/or with water gelatingpolysaccarides such as hyaluronic acid, chitosan and/or fucose richpolysaccharides available, e.g., as Fucogel®1000 (CAS-Nr. 178463-23-5)from SOLABIA S. The moisterzing agent is optionally present in an amountvarying from about 0.5 wt % to about 8 wt. %, preferably from about 1wt. % to about 5 wt. % of the total weight of the composition.

Suitable neutralizing agents may also be included into the compositionof the present invention such as emulsifiers, foam builders andstabilizers. Suitable neutralizing agents include alkali hydroxides suchas sodium or potassium hydroxide; organic bases such as diethanolamine,triethanolamine, aminomethyl propanol, trisodiumethylenediaminetetraacetic acid; basic amino acids such as arginine andlysine; and any combination of any of the foregoing. The neutralizingagent is optionally present in an amount from about 0.01 wt. % to about8 wt. %, preferably from 1 wt % to about 5 wt. %, of the total weight ofthe composition.

The addition of electrolytes into the composition of the presentinvention is preferred to change the behavior of a hydrophobicemulsifier. Thus, the microemulsions of this invention containpreferably electrolytes of one or several salts with anions includingbut not limited to chlorides, sulfates, carbonates, borates andaluminates. Other suitable electrolytes can be on the basis of organicanions such as, but not limited to, lactates, acetates, benzoates,propionates, tartrates and citrates. Preferred cations are ammonium,alkylammonium, alkali metals, magnesium, iron and zinc ions.Particularly preferred salts are potassium and sodium chloride,magnesium sulfate, zinc sulfate and mixtures thereof The electrolytesare present in an amount varying from about 0.01 wt. % to about 8 wt. %of the total weight of the composition.

The compositions according to the present invention are useful forphotoprotecting the human epidermis or hair against the damaging effectof ultraviolet irradiation, as antisun/sunscreen compositions or asmakeup products. Such compositions can particularly be provided in theform of a lotion, a thickened lotion, a gel, a cream, a milk, anointment, a powder or a solid tube stick and can optionally be packagedas an aerosol and can be provided in the form of a mousse, foam or aspray. They can be in the form of a suspension or dispersion in solventsor fatty substances, or alternatively in the form of an emulsion,preferably of the O/W type, such as a cream or a milk, a vesiculardispersion, in the form of an ointment, a gel, a solid tube stick or anaerosol mousse. The emulsions can also contain anionic, nonionic,cationic or amphoteric surfactants.

When the cosmetic compositions according to the invention are used forprotecting the hair, they can be in the form of a lotion, a gel or arinse out composition like a shampoo or a conditioner, to be appliedbefore or after shampooing, before or after dyeing or bleaching, before,during or after permanent-waving or hair straightening operation, astyling or treatment lotion or a gel, a blow-drying or hairsettinglotion or gel, a hair lacquer, or a composition for permanent-waving,straightening, dyeing or bleaching the hair.

The invention is further illustrated by the following examples.

EXAMPLE 1 2-(4-Benzoxazol-2-yl-benzylidene)-malonic acid diethyl ester

a) Diethyl-p-carboxy-benzalmalonate

A 500 ml three necked reaction flask, equipped with a reflux condensercombined with a water separator and an oil bath with a magnetic stirrerwas charged with 24.8 g (170 mmol) of 4-carboxy-benzaldehyde (Fluka),26.3 g (170 mmol) of diethylialonate, 1.3 g of morpholine and 1.4 g ofp-toluene-sulfonic acid in 300 ml of toluene. After two hours underreflux 3 ml of water were separated. The reaction mixture was dilutedwith ethylacetate and washed with aqueous NH₄Cl and NaCl solutions,dried with Na₂SO₄ and concentrated to yield a brown honey.Recrystallization from toluene furnished 18 g of brown crystals. M.p.100-102° C. UV(ethanol) 286 nm (E=24′800)

b) 2-(4-Benzoxazol-2-yl-benzylidene)-malonic acid diethyl ester

10 g of phosphorpentoxide, 25 ml of hexamethyldisiloxane and 50 ml of1,2-dichlorobenzene were mixed in a 250 ml round bottom flask andrefluxed for a few minutes, until the mixture became clear.

1.5 g of the diethyl-p-carboxy-benzalmalonate obtained above and 0.66 gof 2-aminophenol were dissolved in 15 ml of the clear phosphorpentoxidemixture and refluxed for four hours. Then the cold reaction mixture wasdiluted with 150 ml of ethyl acetate and extracted with in NaOH andaqueous NaCl solutions. The organic phase was dried with Na₂SO₄ andconcentrated to yield 1 g of brown crystals, which there chromatographedthrough silicagel in hexane:ethylacetate=3:1, v/v). 0.77 g of product inform of yellow crystals were obtained. M.p. 99-102° C. UV(CH₂Cl₂)331 nm(E=1010); MS: 365 (M⁺), 320, 291, 275, 247, 219 (100%).

Solubility Measurement

An excess of the UV sunscreen was placed in a flask, containing CétiolLC (cocoyl caprylate caprate) and Crodamol DA (diisopropyl adipate),respectively. The suspension was mixed and treated in an ultrasound bathfor 10 minutes. After standing at room temperature for 18 hours, thesolution over the remaining crystals was filtered through a milliporemicrofilter (pore size of 0.45 μm). The concentration of this saturatedsolution was determined by means of UV spectroscopy in comparison with acalibration curve.

The solubility of this product was found to be 4.5% in Cétiol LC and 11%in Crodamol DA.

Photostability:

The photostability is measured in an on-line system Hg-lamp/HPLC, usinga 150 W Hg-lamp of Heraeus with Pyrex filter (2.3 mm) and a Tefloncapillary tube with 0.3 mm inside diameter and a total length of 10 m.3.6. mg of the sample is dissolved in 16 ml of MeOH and 10 μl of thissolution injected. The degradation products are not separated.UV-absorption at a wavelength of 358 nm of the irradiated solution ismeasured periodically up to 14 minutes and the result is compared withthe corresponding photostability of butyl methoxy dibenzoylmethane. Theproduct was detected in >90%, indicating photostability, whereas only16% of butyl methoxy dibenzoylmethane could be detected after 14 minutesof irradiation.

Alternatively, the measurement is performed according to the protocoldescribed in the International Journal of Cosmetic Science 18, 167-177(1996).

EXAMPLE 2 2-Cyano-3-{4-[5-tert.-butyl-benzoxazol-2-yl]-phenyl}-acrylicacid 2-ethylhexyl ester

a) 2-Cyano-{p-carboxy-phenyl}-acrylic acid 2-ethylhexyl ester

A 250 ml three necked reaction flask, equipped with a reflux condensercombined with a water separator and an oil bath with a magnetic stirrerwas charged with 3.8 g (25 mmol) of 4-carboxy-benzaldehyde (Fluka), 6.8g (33 mmol) of cyanacetic-acid-2-ethyl-hexylester, 0.3 g ofbis-(2-hydroxypropyl)-amine and 0.25 g of p-toluene-sulfonic acid in 80ml of toluene and 20 ml of dimethylformamide. After 22 hours underreflux the reaction mixture was diluted with toluene and washed withaqueous NH₄Cl and NaCl solutions, dried with Na₂SO₄ and concentrated toyield 6.2 g (74%) of whire crystals. M.p. 159-162° C. W(CH₂C₂) 305 nm(E=811).

b) 2-Cyano-3-{4-[5-tert.-butyl-benzoxazol-2-yl]-phenyl-}-acrylic acid2-ethylhexyl ester

3.6 g of the 2-cyano-{p-carboxy-phenyl}-acrylic acid 2-ethylhexyl esterobtained above and 2.5 g of 2-amino-4-tert.-butyl-phenol were dissolvedin 16 ml of the clear phosphorpentoxide mixture (described in Example1b) and refluxed for four hours. Then the cold reaction mixture wasdiluted with 100 ml of chloroform and 3× extracted with In NaOH and 1×with aqueous NaCl solution. The organic phases were dried with Na₂SO₄and concentrated to yield a brown honey, which was washed with pentaneand dried under high vacuum. 1.02 g of brown crystals of product wereobtained. M.p. 80-81° C. UV(CH₂C₂) 363 nm (E=816); MS: 458 (M+),443(100%), 409, 346, 331.

The solubility of this product was determined in Cétiol LC=3.8% and inCrodaMol DA=7.4%. The product was irradiated in high dilution with aHg-lamp 150 W from Heraeus and has been shown to be photostable.

EXAMPLE 3 2-(4-Benzoxazol-2-yl-benzylidene)-malonic acid dibutyl ester

a) 2-p-Toluyl-benzoxazole

A 350 ml three necked reaction flask was charged under nitrogenatmosphere with 40.8 g of p-toluylic acid, 33 g of o-aminophenol and 1.5g of H₃BO₃ in 120 ml of diethyleneglycol-diethyl ether and 30 ml ofdiethyleneglycol-dibutyl ether. This mixture was heated first to 180°C., until a slow distillation starts. Then it was heated further to 220°C. for 10 hours, until practically no starting material was visible onthe tlc. At this stage 90 ml of the solvent was distilled off. The cold,crystalline residue-was dissolved in ethylacetate and washedsubsequently with in NaOH, In HCl and saturated aqueous NaCl. Theorganic phase was dried and concentrated. The crystalline material waswashed with hexane and dried under high vacuum to yield 29.5 g of browncrystals. M.p. 104-105° C. UV: (CH₂Cl₂) 303 nm (E=1323).

b) 4-Benzoxazol-2-yl-benzaldehyde

A 750 ml round bottom flask equipped with a magnetic stirrer, a refluxcondenser and an ice cooling bath under nitrogen atmosphere was chargedwith 22 g of 2-p-toluyl-benzoxazole dissolved in 200 ml of aceticanhydride. This mixture was cooled to −5° C. and 44.5 ml of concentratedsulfuric acid was slowly added by means of a dropping funnel, while thetemperature was kept below 0° C. Then a solution of 15.3 g ofCrO₃dissolved in 200 ml of acetic anhydride was slowly added at the sametemperature. The green mixture was left over night with stirring andthen poured on ice. The precipitate was filtered off, washed with waterand dried under high vacuum to yield 18.6 g of aldehyde in crystallineform, containing some traces of starting material. M.p. 162-163° C.UV(CH₂Cl₂) 324 nm (E=1233).

When the reaction mixture was immediately worked up after the additionof the CrO₃ solution, mainly (ca. 73% content)4-benzoxazol-2-yl-benzaldehyde-diacetylacylal was obtained. UV(CH₂Cl₂)302 nm (E=964).

c) 2-(4-Benoxazol-2-yl-benzylidene)-malonic acid dibutyl ester

A 50 ml three necked reaction flask, equipped with a reflux condensercombined with a water separator and an oil bath with a magnetic stirrer,was charged with 2.3 g (10 mmol) of 4-benzoxazol-2-yl-benzaldehyde, 2.6g (1.1 mmol) of di-n-butylmalonate, 0.25 ml of morpholine and 0.17 g ofp-toluene-sulfonic acid in 30 ml of xylene. After five days under refluxmainly the desired product was detected with HPLC. The reaction mixturewas diluted with ethylacetate and washed with water and NaCl solution,dried with Na₂SO₄ and concentrated to yield 4.9 g of a brown honey.Chromatography in hexane/ethylacetate (9:1 to 1:1, v/v) and furnished1.5 g of a yellow liquid. UV(ethanol) 329 nm (E=758), MS: 421 (M⁺,100%).

This product is miscible with Cétiol LC. It was irradiated in highdilution with a Hg-lamp 150 W from Heraeus and has been shown to bephotostable.

EXAMPLE 4 2-Cyano-3-{4-benzoxazol-2-yl-phenyl}-acrylic acid 2-ethylhexylester

A 50 ml three necked reaction flask, equipped with a reflux condenserand an oil bath with a magnetic stirrer was charged with 2 g of4-benzoxazol-2-yl-benzaldehyde-diacetylacylal (73% product content,described in Example 3b), 1.0 ml of cyanacetic-acid-2-ethyl-hexylesterand 0.31 g of dry ZnCl₂ in 15 ml of toluene. This mixture was heated for20 hours to 50° C. Then water and NaOH was added to reach a pH of 9. Theorganic phase was diluted with ethylacetate and washed with water andNaCl solution, dried with Na₂SO₄ and concentrated. The residue waschromatographed in hexane/ethylacetate (9:1 to 1:1, v/v) and thenrecrystallised from hexane and toluene and furnished 0.7 g of yellowishcrystals of 2-cyano-3-{4-[benzoxazol-2-yl]-phenyl}-acrylic acid2-ethylhexyl ester. M.p. 84-85° C.; UV(CH₂Cl₂) 355 nm (E=964); MS: 402(M⁺), 290 (100%), 273, 246.

The solubility of this product was determined in Cétiol LC=1.6% and inCrodamol DA=2.8%. The product was irradiated in high dilution with a.Hg-lamp 150 W from Heraeus and has been shown to be photostable afterE/Z isomerisation.

EXAMPLE 5 3-{4-Benzoxazol-2-yl-phenyl}-2-propionyl-acrylic acid2-ethylhexyl ester

The same reaction as in Example 4 was performed, but instead ofcyanacetic-acid-2-ethyl-hexylester, ethyl-3-oxo-valerate was used. Afterchromatography an E- and a Z-product was obtained. Data of theZ-product: M.p. 82-83° C.; UV(CH₂Cl₂) 334 nm (E=1083); MS: 349 (M⁺),334, 320 (100%), 292, 252.

The product eras irradiated in high dilution with a Hg-lamp 150 W fromHeraeus and has been shown to be photostable after E/Z isomerisation.

EXAMPLE 6 2-(4-[6-Hydroxy-benzoxazol-2-yl]-benzylidene)-malonic aciddiethyl ester

The same reaction was performed as in Example 1b, but instead of2-aminophenol, 4-amino-resorcinol was applied. Instead ofchromatography, the raw material was recrystallised three times fromacetonitrile, hexane and CH₂Cl₂ to yield 12% of yellow crystals. M.p.153-55° C. UV(CH₂Cl₂) 346 nm (E=851); MS: 381 (M⁺, 100% 336, 307, 291,263, 235.

The solubility of this product was determined in Crodamol DA=1.6%. Theproduct was irradiated in high dilution with a Hg-lamp 150 W fromHeraeus and has been shown to be photostable.

EXAMPLE 72-(4-[6-{2-Ethyl-hexyloxy-benzoxazol-2-yl]-benzylidene)-malonic aciddiethyl ester

A 50 ml three necked reaction flask, equipped with a reflux condenserand an oil bath with a magnetic stirrer was charged with 0.7 g of2-(4-[6-hydroxy-benzoxazol-2-yl]-benzylidene)-malonic acid diethyl ester(described in Example 6), 0.34 ml of 2-ethyl-hexyl-1-bromide and 0.5 gof anhydrous. Na₂CO₃ in 10 ml of 1-methyl-2-pyrrolidone. A trace ofeach, KJ and tetrabutylammonium-sulfate was added, After 20 hours at100° C., no starting material could be seen on the tlc. The reactionmixture was diluted with ethylacetate and washed with InNaOH, water andNaCl solution, dried with Na₂SO₄ and concentrated. Then it waschromatographed in hexane/ethylacetate (9:1 to 1:1, v/v) and furnished300 mg of light yellow crystals. M.p. 50-52° C.; UV(ethanol) 352 nm(E=695); MS: 493 (M⁺), 381 (100%), 307, 235.

The solubility of this product was determined in Cétiol LC (Cocoylcaprylate caprate)=10.2% It was irradiated in high dilution with aHg-lamp 150 W from Heraeus and has been shown to be photostable.

EXAMPLE 82-(4-{6-[2(2-Ethoxy-ethoxy)ethoxy-benzoxazol-2-yl}-benzylidene)-malonicacid diethyl ester

The same reaction was performed as in Example 7, but instead of2-ethyl-hexyl-1-bromide, 2-(2-ethoxy-ethoxy)-ethoxy-methylsulfonate wasapplied. After work up the product was chromatographed withhexane/diethylether (9:1 to 1:1, v/v) to yield a yellowish oil, whichcrystallised only after a two months time. M.p. 43-45° C.; UV(CH₂Cl₂)341 nm (E=551); MS: 497 (M⁺, 100%). 452, 381.

The solubility of this product was determined in Cétiol LC=4.6%. Theproduct was irradiated in high dilution with a Hg-lamp 150 W fromHeraeus and has been shown to be photostable.

EXAMPLE 92-(4-{6-[2-(Methyl-bis-(trimethyl-silyloxy)-silyloxy)-prop-2-enyloxy]benzoxazol-2-yl}-benzylidene)-malonicacid diethyl ester

a) 2-(4-[6-{2-Propargyloxy}-benzoxazol-2-yl]-benzylidene)-malonic aciddiethyl ester

The same reaction was performed as in Example 7, but instead of2-ethyl-hexyl-1-bromide, propargylbromide was applied. After work up theproduct was chromatographed with hexane/ethylacetate (9:1 to 1:1, v/v)to yield yellow crystals. M.p. 105-107° C.; UV(CH₂Cl₂) 345 nm (E=875);MS: 419 (M⁺), 380 (100%), 374, 306, 234.

b)2-(4-{6-[2-(methyl-bis-(trimethyl-silyloxy)-silyl)-prop-2-enyloxy]-benzoxazol-2-yl}-benzylidene)-malonicacid diethyl ester (hydrosilylation reaction)

200 mg of the2-(4-[6-{2-propargyloxy}-benzoxazol-2-yl]-benzylidene)-malonic aciddiethyl ester (Example 9a, above), 125 mg of 1,1,1,3,5,5,5-heptamethyltrisiloxane and a catalytic amount of divinyl-tetramethyl disiloxaneplatinum complex in 5 ml of toluene was placed in a three-neckedreaction flask under inert atmosphere, stirred for 20 hours at 80° C.and then two days under reflux. The product solution was washed with amixture of water/methanol, 1:10, v/v and concentrated. This product waschromatographed in hexane/ethylacetate 9:1, v/v to yield a honey-likeliquid. WV 348 nm (E=535). NMR showed a mixture of the vicinal and thegeminal hydrosilylation product=1.3. It has an unlimited solubility inthe cosmetic solvents tested above and excellent photostabilityqualities in high dilution.

EXAMPLE 10 A Polysiloxane Which Corresponds Statistically to theFollowing Formula

200 mg of the2-(4-[6-{2-propargyloxy}-benzoxazol-2-yl]-benzylidene)-malonic aciddiethyl ester (Example 9a, above), 530 mg of polysiloxane Ae-151 ofWacker-Chemie GmbH and a catalytic amount of platinum on carbon 5% in 10ml of xylene was placed in a three-necked reaction flask under inertatmosphere and heated for five days to 120° C. The product solution wasfiltered through Cellite, washed with a mixture of water/methanol, 1:10,v/v and concentrated to yield a brownish oil. UV 348 nm (E=207), havingunlimited solubility in Cétiol LC and Crodamol DA and excellentphotostability qualities in high dilution.

EXAMPLE 11 Preparation of a O/W Sunscreen Lotion UV-B and UV-A

Broad spectrum sunscreen lotion containing 2% of the compound of Example1.

Recipe % Compound Chemical Name Part A 2 PARSOL MOX Ethylhexylmethoxycinnamate 2 Product of Example 1 3 PARSOL 17894-t-Butyl-4′-methoxy-dibenzoyl- methane 12 Cétiol LC Cocoyl-caprylatecaprate 4 Dermol 185 Isostearyl neopentanoate 0.25 PEG-2-stearateDiethyleneglycol monostearate 1 Cetylalcohol Cetylalcohol 0.25 MPOB/PPOBMethyl-propylparabene 0.1 EDTA BD EDTA-sodium salt 1 Amphisol DEA(Givaudan) Diethanolamine cetylphosphate Part B 0.2 Permulene TR-1Acrylate C10-C30 Alkylacrylate 68.4 Water deionized 5 Propyleneglycol1,2-Propanediol 0.8 KOH (10%) Potassium hydroxide

Part A is heated in a reactor to 85° C.

Part B is slowly added within 10 minutes, followed by addition of KOH,cooling and degassing of the emulsion.

EXAMPLE 12 Preparation of a High Protective Sun Milk

Ingredients NCI Nomenclature % w/w A) PARSOL SLX Dimethico 6.00Diethylbenzalmalonate PRODUCT OF 6.00 EXAMPLE 10 Parsol 50004-Methylbenzylidene camphor 4.00 Parsol MCX Ethylhexyl methoxicinnamate6.00 Uvinul T 150 2.00 Silicone DC 200/350 cs Dimethicone 1.00 Lanette OCetyl alcohol 2.00 Softisan 100 Hydrogenated coco-glycerides 3.00Tegosoft TN C12-15 Alkyl benzoate 6.00 Cetiol B Dibutyl adipate 7.00Vitamin E acetate Tocopheryl acetate 2.00 Berkemyol (Grape Seed)Palmitoyl grape seed extract 1.00 BHT BHT 0.05 Edeta BD Disodium EDTA0.10 Phenonip Mixture of phenoxyethanol, 0.60 methylparaben,ethylparaben, propylparaben and butylparaben AMPHISOL K Potassium cetylphosphate 2.00 B) Water deionized 44.45 Propylene Glycol Propyleneglycol5.00 Carbopol 980 Carbomer 0.30 C) KOH (10% sol.) Potassium hydroxide1.50

1. A compound of general formula I

wherein R¹ and R² are, independently from each other, hydrogen; halogen;hydroxy; (C₁-C₂₀)-alkyl; (C₂-C₂₀)-alkenyl; or (C₁-C₂₀)-alkoxy; X isoxygen or an imino group, optionally substituted with R¹; R³ and R⁴ are,independently from each other, cyano; —COOR⁵; —COR⁶; —CONH₂; —CONHR⁷; or—CONR⁸R⁹; R⁵, R⁶, R⁷, R⁸ and R⁹ are, independently from each other,hydrogen; (C₁-C₂₀)-alkyl, wherein one or more methylene groups areoptionally replaced by one or more oxygens; (C₁-C₂₀)-haloalkyl;(C₂-C₂₀)-alkenyl, optionally substituted by tri-(C₁-C₅)-alkylsilyl,triphenylsilyl or a group —Si[CH₃]_(n)[OSi(CH₃)₃]_(3-n), wherein n is 0,1, 2 or
 3. 2. A compound according to claim 1 wherein X is O.
 3. Acompound according to claim 1 wherein R¹ and R² are hydrogen.
 4. Acompound according to claim 1 wherein R³ cyano and R⁴ is —COOR⁵.
 5. Acompound according to claim 4 which is:2-cyano-3-{4-[5-tert.-butyl-benzoxazol-2-yl]-phenyl}-acrylic acid2-ethylhexyl ester or 2-cyano-3-{4-benzoxazol-2-yl-phenyl}-acrylic acid2-ethylhexyl ester.
 6. The compound according to claim 1, wherein R³ andR⁴ are, independently from each other, —COOR⁵.
 7. A compound accordingto claim 6 which is: 2-(4-benzoxazol-2-yl-benzylidene)-malonic aciddiethyl ester; 2-(4-benzoxazol-2-yl-benzylidene)-malonic acid dibutylester; 3-{4-benzoxazol-2-yl-phenyl}-2-propionyl-acrylic acid2-ethylhexyl ester;2-(4-[6-hydroxy-benzoxazol-2-yl]-benzylidene)-malonic acid diethylester; 2-(4-[6-{2-ethylhexyl-oxy}-benzoxazol-2-yl}-benzylidene)-malonicacid diethyl ester; or2-(4-[6-[2-(2-ethoxy-ethoxy)-ethoxy]-benzoxazol-2-yl}-benzylidene)-malonicacid diethyl ester.
 8. A composition comprising a compound according toclaim 1 and at least one pharmaceutically and/or cosmetically acceptableexcipient.
 9. A composition according to claim 8, wherein the compoundaccording to claim 1 is present in an amount varying between 0.5 and 20%by weight of the total amount of the composition.
 10. A compositionaccording to claim 9 wherein the compound according to claim 1 ispresent in an amount varying between 0.5 and 12% by weight of the totalamount of the composition.
 11. A composition according to claim 8 whichis a topical composition.
 12. A composition according to claim 9 whichis a topical composition.
 13. A composition according to claim 10 whichis a topical composition.
 14. A method for protecting human skin orhuman hair from UV-A irradiation comprising applying a photoprotectiveamount of a compound according to claim 1 to the human skin or humanhair.
 15. A method for protecting a plastic material or a medicinalproduct that is sensitive to UV radiation from UV-A irradiationcomprising applying a photoprotective amount of a compound according toclaim 1 to the plastic material or medicinal product.